Q3 2021 Cymabay Therapeutics Inc Earnings Call
[music].
Good day, ladies and gentlemen, and welcome to FEMA based third quarter 2021 financial results and business update conference call. At this time all participants are in a listen only mode. Following the formal remarks, we will open the call for your questions. Please be advised that the call will be recorded that at the <unk>.
These requests it is also being webcast live on the investors section at <unk> website at Www Dot seem a bay dot com.
Now I'd like to turn the call over to Mr. Paul Quinlan General Counsel at Sema Bay. Mr. Quinlan. Please proceed.
Thank you operator, and good afternoon, everyone I hope that you've had a chance to review the press release, we issued announcing our third quarter 2021 financial results and business update.
You can access that release on our website under the investors tab.
Joining me on the call today are Soochow Shah Chief Executive Officer, Dr. Chuck Mcwherter, Chief Scientific Officer, and Dr. Dennis Kim Chief Medical Officer.
Following our prepared remarks, we will open up the call for Q&A.
Before we begin I'd like to remind everyone that statements made during this conference call, including the Q&A session relating to sema bays expected future performance.
Business prospects events or plans, including clinical plans.
Regulatory approval funding and repayment schedule and anticipated timelines and trial enrollment date.
Cash runway and planning for commercialization of any future products are forward looking statements as defined under the private Securities Litigation Reform Act of 1995.
Although the company believes that the expectations reflected in such forward looking statements are based upon reasonable assumptions actual outcomes and results are subject to risks and uncertainty.
Could differ materially from those forecast due to the impact of many factors. The company assumes no obligation to update or supplement any forward looking statements.
As a result of new information future events or otherwise, except as required by applicable law.
Participants are directed to the cautionary statements set forth in today's press release as well as the risk factors set forth in Sema base quarterly and annual reports filed with the SEC for factors that could cause actual results to differ materially from those anticipated in the forward looking.
<unk>.
This conference call is the property has seen a day and any recording or rebroadcast is expressly prohibited without the written consent of seen a day.
At this time I'd like to turn the call over to schedule.
Thank you Paul good afternoon, and thank you for joining us today.
The third quarter marked another period of significant progress at Sema Bay toward achieving our mission of improving the lives of patients with the rare autoimmune inflammatory liver disease primary biliary cholangitis or PBC.
Since restarting Philadelphia our development.
We have strengthened and grown our team and in this quarter have achieved many of our operating plan objectives and clinical development manufacturing and commercial planning.
Our team is working towards completing what we believe is the most extensive development program for any investigational drug in PBC.
In addition to our previously completed phase III in hand and.
And multi year open label studies.
Our program is back on track.
And we are currently executing five clinical studies with zelle, Adele par in more than 20 countries and across five continents in support of our plan for a robust NDA submission.
The twin pillars of this effort our two global studies in patients with PBC.
Response, the primary phase III efficacy and safety study to support marketing approval and is sure a long term safety study to complete a comprehensive patient safety database.
Today, our comments will provide a brief summary of our operational progress.
With our ongoing clinical studies.
Additional data being presented for the first time later this week at the liver meeting sponsored by the American Association for the study of liver diseases.
And a summary of our third quarter financials.
Before Denison Chuck discussed our ongoing studies in upcoming presentation at the liver meeting I think this is a good time to give those not familiar with solid albar and appreciation for the breadth and depth of our experience in PBC.
And the confidence this has given us that sell Adele par has the potential to be a leading treatment option for many patients with PBC.
Before discussing the cell Adele Bar program, let me lay out what we see as the three main unmet needs for patients with PBC.
First many patients need therapies with improved activity against the disease as evidenced in the incomplete responses, commonly observed in their liver lab tests for cholestasis and liver injury.
These tests include levels of alkaline phosphatase bilirubin and transaminase.
Biomarkers that have been associated with histological progression and poor outcomes for patients with PBC.
It can be argued that offering patients an improved biochemical response, and especially the opportunity to potentially achieve the ideal response of biochemical normalization should be a goal of therapy in PBC.
Second many patients with PBC suffer from significant burden of symptoms, including pure writers.
Currently approved therapies have not address this need and the only approved second line treatment of better coal or gas. It has been associated with exacerbation or worsening of pruritus.
A therapy that can provide symptom relief would improve patients' lives potentially improving acceptability and adherence to therapy as well.
Lastly, the majority of PBC patients encompass a spectrum of disease stage, ranging from those without cirrhosis to those with compensated cirrhosis, including with portal hypertension.
A leading treatment option should be safe across the spectrum of non cirrhotic in compensated cirrhotic stages of disease.
Beginning in 2015, we initiated a series of studies of <unk> in patients with PBC.
That have now included more than 400 participants and has explored a wide range of cell Adele part doses from two to 200 milligrams.
Over 50 patients in these studies have been treated for two years or more.
A remarkably consistent profile has developed across the open label Phase II studies, and the placebo controlled enhance phase III study.
The 10 milligram dose emerged as the optimal dose with a pattern of rapid and sustained response with 70% to 80% of patients achieving the primary endpoint.
Which includes alkaline phosphatase and bilirubin that has been used for accelerated approval of second line treatment in PBC.
Further up to 30% of patients on seller dalbar normalize their levels of alkaline phosphatase, a potentially significant improvement over available second line treatment.
Significant decreases in transaminase as well.
Were also found and we believe that these may be an important difference from other drugs currently in development.
As described in our recent publication in the journal liver International.
The 10 milligram dose appears to have improved pruritus.
Sleep and fatigue, while lowering serum bile acid levels after 52 weeks of treatment.
This effect on pure itis was consistent with the data in hand.
Which was measured after three months of treatment using an E diary collection on the purest numerical rating scale.
In June we reported a comparison of the efficacy and safety in a pooled analysis of patients with and without cirrhosis.
Finding that the biochemical responses and safety profiles were similar in the subpopulation.
Taken together the treatment effects on alpine phosphatase, bilirubin transaminase and pure writers.
Cross non cirrhotic and cirrhotic stages support what appears to be a safe and well tolerated profile and is encouraging for our efforts to confirm this in their response and assure studies as part of the expected NDA submission package.
I'd like to ask Dennis to turn our attention to the progress we've made toward enrolling our phase III response, and long term sure studies Dennis.
Yeah.
Thank you for you Joe.
I will remind you that we had we initiated a global phase III registration study response in the first quarter of this year.
Randomized our first patient in April.
Responses, a 52 week placebo controlled randomized global phase III registration study.
Evaluating the safety and efficacy of citadel par in patients with PBC.
The study is intended to enroll 180 patients.
Two to one randomization to oral once daily fell adult part 10 milligrams or placebo as an add on therapy to patients with an inadequate response or are intolerant to first line Arthur deoxycholic acid therapy.
The primary outcome measures is the composite biochemical responder rate after 52 weeks for Auckland phosphatase and bilirubin.
The same endpoint used to register a caliber.
The only approved second line treatment alternative for PBC.
And the same endpoint from our initial phase III study enhance.
Two key secondary endpoints that we also studied and enhance and will evaluate and response include the rate of normalization of alkaline phosphatase at 52 weeks and improvements in pruritus from baseline for six months in patients with moderate to severe pruritus as reflected.
And baseline pruritus numerical rating scale value of four or greater.
As usual highlighted our extensive operational experience in PBC continues to be a tremendous asset.
Particularly in the face of the challenges are our entire industry has faced conduct a clinical study during the global COVID-19 pandemic.
We have mentioned previously the headwinds we have faced including longer approval time for investigational review Board and ethics committees required prior to contracting with sites and Resourcing challenges that sites.
Which have increased timeline for site activations in screening.
We continue to offer patients.
And sites a wide range of alternatives to make it easier on patients to participate in our studies.
Years of building relationships with sites staff investigators and patient advocacy groups and sharing results from our previous studies continues to pay off.
On our last quarterly call, we had approximately 40 active sites in 10 countries.
Today, we have more than 100 sites in more than 20 countries activated to screen and enroll patients with more expected to be activated before the end of the year.
In our rare disease, such as PVC, where it is not uncommon to enroll one to two patients per site on average.
This critical mass of activated sites.
Key to driving an accelerated enrollment.
Which we expect to be completed in the first half of 2022.
Yeah.
In addition to making progress in response site activation and enrollment in our assuring long term study of cells Alpine patients with PBC also continues to accelerate.
Well sure is opened to PBC patients enrolled in previous studies themselves El par.
Like response, it will be conducted in more than 20 countries and has already activated more than 50 sites with more than 90% of patients completing screening having enrolled.
It is understandable that.
With the emphasis placed on response assure is sometimes overlooked.
But to our knowledge sell at El <unk> is the only investigational study drug in development for PBC that has dedicated and significantly sized.
Long term study like assure providing our value of study patients an opportunity to receive chronic treatment would sell about par.
As well as our investigators with crucial sells up our clinical experience.
In our view not only does this significantly support the approval decisions that regulatory regulators will make but.
But we believe it will provide a rich and significant source of persuasive information to inform practice guidelines.
Here's physicians and patients as they select treatment options.
Let me hand, the call over to Chuck to discuss our upcoming clinical abstracts and presentations that will be featured at the liver meeting this week Chuck.
Thank you Dennis.
The extensive clinical program to date continues to give us additional ways to examine and understand seller <unk> profile.
Continuing our commitment to research we're pleased to have two important and revealing analyses to report at the upcoming AA S. L D liver meeting.
An oral presentation will be made by Dr. Marlin mile.
Professor of internal Medicine division of digestive and liver diseases at the University of Texas, Southwestern and Dallas, Texas.
Dr. <unk>, a prominent expert in PBC and an investigator in our studies will discuss the efficacy and safety of sell adult par during two years of treatment in patients with PBC.
The mean percent change in alkaline phosphatase from baseline was minus 42% at one year.
And further improved to minus 50% and the more than 50 patients treated for two years.
Over two years, there were sustained reductions in the transaminase is a L. TNA S. T that are commonly associated with inflammation and liver injury and a gamma glutamyl transferase, a biomarker associated with cholestasis and oxidative stress.
In this analysis of two year data.
<unk> appeared safe and well tolerated.
These results support an interpretation that long term treatment with cell Adele par results and continued improvement in markers of cholestasis and risk for disease progression.
We believe that sell at El <unk> is the only drug in development for PBC as an add on therapy to you DCA that has safety and efficacy results of this duration.
And a second presentation, Dr. Cynthia Levy assistant director for the shifts center for liver diseases and program director for the transplant Herpetology Fellowship at the University of Miami, and Florida will discuss a pooled analysis from sell auto par phase II and phase III studies examining its efficacy Ann.
Safety in patients with compensated cirrhosis and evidence of portal hypertension due to PBC.
This electronic poster presentation will highlight the effects of cell it apart in compensated cirrhotic patients with portal hypertension after three months of treatment.
This led to alkaline phosphatase changes of minus 30% and the five milligram group.
And minus 45% in the 10 milligram group.
Total bilirubin platelets in albumin, either improved or remained stable.
Again in this analysis sell adult <unk> appeared safe and well tolerated.
The efficacy safety and Tolerability in patients with compensated cirrhosis in portal hypertension was comparable to that of non cirrhotic patients.
Portal hypertension in cirrhotic patients with PBC is estimated to comprise about half of all patients who have compensated cirrhosis.
Portal hypertension is a significant risk factor for progression to decompensation, which are liver related adverse events.
Patients with cirrhosis and portal hypertension have narrowing treatment options. After the recent restriction for their treatment with the FDA to revisions to the Ocala that label.
Understanding the safety and efficacy of sell it at par in cirrhotic patients with and without portal hypertension.
Ongoing part of the sell adult par program.
With the goal of understanding to sell adult par is an appropriate treatment option for this currently unserved populations.
For those who are unable to attend the liver meeting.
We will be hosting an encore webcast of these two presentations with Doctor Smile and Levy on Monday November 15 at 430 P M Eastern time.
Information to access the live webcast of this post a a S. L. D. K O alcohol is contained in the press release, we issued today.
And a link will also be available on the events section of the <unk> website.
As soon as Joe mentioned earlier.
Fear reviewed paper was published in August in liver International and its co authors includes six leading experts in Cola static pruritus.
It reported that sell at El <unk> appeared to improve pruritus over 52 weeks as assessed by three independent questionnaires.
This baseline intensity correlated with serum bile acid levels and pruritus improvement over 52 weeks correlated with decreases in a specific set of serum bile acids.
This paper also reported improvements in patient reported sleep disturbance using two different questionnaires and.
And improvements in fatigue scores using the PBC 40 questionnaire.
The study has limitations and that is not placebo controlled but this is mitigated by the significant agreement between the different measures of pruritus and the persistence of the effect through 52 weeks.
You can find a link to this publication on our website.
The enhanced study.
<unk> important confirmation of these pruritus effects and we will seek to further confirm them and the response study.
Once again Sema Bay remains committed to sharing and publishing results from our clinical studies.
Joe.
Thank you Chuck.
Before we open the call for questions. Let me review some of our key financials for the third quarter.
As of September 30th our head Count grew to 54 employees as we successfully recruited key team members and clinical regulatory and medical affairs.
Net loss for the three months ended September 30th 2021 and 2020.
It was $22 7 million and $11 $4 million.
Or <unk> 33, and 17 cents per diluted share respectively.
Net loss for the nine months ended September 32021 and 2020.
It was $63 $5 million and $35 $2 million or <unk> 92.
And 51 per diluted share respectively.
Net loss during the three and nine months ended September 32021 was higher than the comparable periods in 2020, largely due to increases in clinical operating expenses.
Which were incurred following the resumption of our clinical development of Philadelphia in PVC during the second half of 2020.
In particular cost increases were primarily driven by enrollment activities associated with response and assure our two active global late stage clinical trials in PBC.
We expect our operating expenses to increase in 2021, as we continue to execute on our clinical development plans and PVC.
We completed the quarter ended September 32021, with cash cash equivalents and short term investments of $113 $8 million.
As we discussed on our prior quarter call in July we signed a non dilutive risk sharing funding agreement with adding worth.
To support the development of cell at Alpine in PBC.
Under the terms of this strategic development funding agreement.
We will receive from adding worth up to $100 million to fund the <unk> development program for PBC.
Of which $75 million will be received over approximately six months from execution of the transaction.
We received the first installment of $25 million during the third quarter.
And the second installment of $25 million last week.
We believe our existing cash.
And investment together with the third $25 million installment under the AB worth agreement that we expect to receive in early February 2022.
We will provide sufficient capital to fund our current operating plan into 2023.
Furthermore, the additional $25 million of development financing available to us at our option upon the completion of enrolment in response would further extend our runway.
We're now happy to take questions.
Operator.
At this time, we'll be conducting a question and answer session. If you would like to ask a question. Please press star one on your telephone keypad confirmation tone will indicate your line is open. The question. Kim you May Press Star two if he would like to remove your question from the queue.
For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys, one moment, please while we poll for questions.
Our first question comes from Yasmin Rahimi with Piper Sandler.
Proceed with your question.
Hi team. This is Jesse on for Yeah. Congrats on your quarter and we just have to question on <unk>.
The first one is now that we.
Umbrella completion or the response study is pushed back to one H 'twenty. Two can you. Please tell us how confident you are that enrollment will remain on track for this timeline on California one.
Okay.
Thank you Jessie further question.
Smiling here, because I wish I was in the game of giving that kind of precision, but let me address your question. This way we knew on our last quarterly call that the pandemic and evolving situations globally with the pandemic, but really put us in a position to keep sites active in enrolling into the first half.
Next year. So we made that announcement on our prior quarterly call. We continue to make significant progress. We are seeing acceleration, we're seeing increases in screening. So we've got a tremendous degree of confidence overall in our ability to execute.
And I think as you and others know in 2019 of course pre pandemic. We were successful in enrolling a global phase III study enhance with 265 patients.
That study took us just under 12 months to fully enroll.
Although we're targeting 80 fewer patients in their response phase III study currently.
We're hopeful that that timeline and the challenges of the pandemic effectively offset the smaller patient population that were enrolling here, but I think at the core of our confidence Jesse really comes from the relationships.
We mentioned we have over 100 sites now active across 20 countries. That's the type of execution. We firmly believe is needed to continue to execute on these timelines. This is a rare disease as you know.
And of course, we're enrolling patients with alcuin phosphatase levels that are elevated after inadequate response to UDC, a largely and so even pre pandemic. The most significant screen failure from this population are really patients, whose outclasses still elevated but below that threshold that is required for regulatory approval.
Now when we think a bit about how we progressed since 2019 in our initial phase III study as I mentioned there is much more experience at sites in the medical community for patients would sell at alpine and that's really where we drive a lot of our confidence of the data that Chubb talked about that we're very excited to share it.
And a great activity and on that note can you guys tell tell us what work has been done on the pier front for pricing.
Jesse Thanks for that question as well. So you know we've been doing actually quite a bit of work thinking about the addressable patient population for Seladelpar of course, it starts with our datasets and is Chuck and Dennis highlighted during the call. You know that data set includes a very robust anti call the static effect.
Really a more meaningful effect than current second line treatment alternatives certainly from our phase two and phase three experience. It demonstrates a significant anti inflammatory benefit as well as an anti paretic benefit and you mentioned the iPad inhibitors of course for very different indications ultra.
Ultra rare pediatric Cola static diseases, where the significant burden of pure riotous for these young children has a significant impact on their quality of life. You know ultimately in the setting of P. B C. You know today. The only currently approved dragging PVC is priced at about 90000, a year and that's a rough.
Estimate of course.
And we think that Seladelpar has the ability to offer patients even greater benefit.
We're seeing that in our datasets and as we continue to do our market research. We continue to have confidence in our ability to really deliver the actual value that would underlie the right pricing at the end of the day. That's how we think about the scenario around thinking about the targeted commercial opportunity in pricing. Obviously, there's work that we will.
Continue to do with the medical community with the Payor community, but we're quite confident in our ability to execute and and actually improve upon again, what's out there today for patients and I think that's really going to be the key driver you saw perhaps last week, you know increases and estimates for a medical.
Like acid.
Revenue estimates for Battle Coke as it now on a run rate north of $350 million a year. This year and I think that really underscores the unmet need for patients and the significant unmet need to reduce their risk of disease progression. So we continue to be emboldened and quite confident in that opportunity and it really builds off of that van.
<unk> per patient as we think about pricing and commercial but it's still early we continue to do that work and will continue to progress as our datasets mature.
Hey, Thank you so much that's all for me and we're excited to see you guys. This weekend.
A S L D I'll jump back to make you.
Thank you Jessie.
Our next question comes from Stevens seat House with Raymond James. Please proceed with your question.
Hi, good afternoon. Thanks revision. The question just the longterm data for solid Gophers, hoping you could comment on how sustained.
Uhm.
Brightest improvements we're in if that state of that will be included in the living room at presentation or have your event.
Monday.
So thank you for that question. This is Chuck.
We're focused in this particular presentation on biochemical response around.
Whoever biochemistry tests basically so both cola static and inflammatory markers as well as safety so crisis won't be part of the story.
As I mentioned earlier on the call we do have.
I think a very impressive study with 52 weeks of data.
Shows that the price decreases fairly quickly within about four weeks and then it sustains out through all of this study visits right out to 52 weeks. So we're not gonna be presenting that data in this particular opportunity, but I don't think there's any reason that that the effects and provide us with a <unk>.
Given the stability you know say from a month all the way through 52 weeks.
The only other thing I would add their Steve is as Chuck had mentioned the publication and liver International that just came out has a significant amount of depth of information overall on symptom burden for patients pruritus fatigue sleep disturbance as well as the relation of those symptoms to bile acid content and.
So I think we hypothesize effectively that if the effects are there on the bile acids and limiting those bile acids, specifically that that should lead to a confidence around a sustained benefit on these symptom burdens.
Yep. Okay. Thanks, Thanks for the color of their good Okay. What else was just on the.
The final $25 million tranche from.
It didn't work.
I mean, it would certainly seem like.
You could probably use the money before even if everything goes well with enrollment.
And first at 22, and and large et cetera, you.
You can use those dollars at some point so what would be to reschedule factors of reasons why you wouldn't draw down on your off in there.
Yeah, It's a great question and absolutely as we mentioned that final 25 million of the up to 100 million from the adding worth clinical co development financing is solely at our discretion at the completion of enrollment you know at the end of the day, Steve I'd say that you know we have continued to have multiple avenues of fund.
<unk> R programs in financing the company I've mentioned this in the past you know we are quite grateful for the investors that we have in the interests that we have in seladelpar, an inseam of a more broadly fundamentally it's just an option. We we like to remain in contain that option ourselves as we think about various ways to fund the company go.
Going forward opportunities to continue to actually show value as our programs progressed and as we continue to have data driving value of events.
I think we want to maintain the optionality for ourselves to finance the company in the right way and we of course think about those decisions wearing the lens of our existing investors. So you're absolutely right. I think it is a great benefit for us to have that additional tranche will ultimately just make that decision based on the best available information at that time.
Thanks, you too I appreciate it thank you.
Yeah.
Our next question comes from Patrick Dulles, All with lifestyle capital. Please proceed with your question.
Hi, Thanks for taking my question so for the a F O D presentation regarding use of Seladelpar in compensated ceramics with evidence of portal hypertension kind of within the backdrop of a label changes rocker. We've could you just remind us if those patient subset will be enrolled into responsible if so.
So could you provide context as to what this would mean for the potential market opportunity. There and then just if you could answer the same question as it relates to the Decompensated cirrhotic population. Thanks.
Yeah, I'll take the first part and I'll, let the soochow step in for the the market the perspective, yeah, so patient and enhance as well as in response are expected.
To have some patience with compensated cirrhosis and portal hypertension, the inclusion criteria.
Would would allow for those that clinical evidence for portal hypertension comes from.
Splenomegaly and thrombocytopenia some of some of those considerations and so we would expect to have probably a comparable representation just to remind you that of about 350 patients enrolled.
In the face too as well as an enhanced by 20% of them had compensated cirrhosis and somewhere somewhere a little south of 50% had evidence of portal hypertension. So there's no reason to believe right now and it remains to be shown that we won't enroll the same population and.
In response, and so it's something that we feel is very important. It's uhm you can have a patient compensated cirrhosis with no no portal hypertension, if they progress and.
And that develops you want to know that your drug is gonna be safe. So that's that's an important consideration and then patients with portal hypertension as I mentioned for.
For a much higher risk for decompensation events, you know either the societies or peritonitis Uhm Ferris wheel believes those kinds of things and once you have an event like that you are at a much significant risk for you know the dire consequences, you're basically on the.
Down downhill slow.
In terms of decompensation, they're currently not in our studies.
They're excluded and I think the reality is that the compensation is a situation where patients are at much higher risk for progression. It's uhm becomes much more challenging to imagine that you'd have a therapeutic intervention that could call progression.
Much less much less reverts it unfortunately and.
Oh, let's soochow talk about their representation in the commercial population, but let's just say it slow yeah.
Yeah, and and and I think Patrick <unk> with some additional comments here that I think are important as you know even though.
It may only be about 10% of those 20% of patients with cirrhosis that Chuck Mencher, maybe even smaller percentage with portal hypertension the diseases of spectrum.
And so of course, there's much more work for us to continue to do as we evaluate this patient population in our ongoing response study expecting against similar percentages.
But you know when you're retraining physician you know that at some point in time, a patient could progress and so having a data set that shows both advocacy as well as importantly safety and the more advanced population I think drives a comfort level for physicians, who have patience, even later stage and disease be compensated Surat.
<unk> or patients that are perhaps on the cusp of.
Of of the coming Cerotic and so given the fact that it's a spectrum. When you can have a safety data set and efficacy in that population I think it drives even greater confidence in the more broad population as it pertains to overall safety.
Super helpful. Thanks again.
Thank you.
Our next question comes from jail Sandwich Open Heimer. Please proceed with care question.
Oh, Hey, thanks for the update and thanks for taking my questions.
Can you talk about what additional steps may be taken to redefine efficacy and the treatment of P. B C. As the normalization about fries and.
Then separately since intercept is working on an O C. A plus there's a fibroid combo for the treatment of P. B C.
Can you talk about any potential seladelpar combinations that you may be considering or potentially have looked at pre clinically.
Thank you.
Yeah. Thank you. Thank you Jay for that question.
Yeah, I think initially J, you're asking about just additional steps with respect to the development normalization, yeah normally F. Yeah. Yeah. Yeah. So just to give you a little bit of color. This is emerging from research this coming from the global PVC study group.
Which is academic consortium that has access to very large pay.
Patient registry of more than 5000 patients, where they've made a connection to a normalization of alkaline phosphatase and its improvement on outcomes.
And so this discussions ongoing in the academic community.
Have become have turned from the previous measures of let's say below 1.67 to look to normalization is what we would call an ideal response.
Every patient it can be argued benefits from <unk> from lowering of their off when phosphatase put the best benefit comes from normalization and so we would expect this to be a continued area of discussion both from sponsors measuring it is and points and monitoring patients for disease progression, but I'll.
Also in the academic community, we I think that there's already a discussion of foot about considering whether practice guidelines should be looked at to address whether normalization should be the ideal cole.
Yeah in L. A dress the second part of your question here a bit J U B O C. A plus b as a firebreak strategy.
I think it's one that makes sense if a patient initially as an O C. Arabetic call a gas that you know we know those patients.
Almost 50% of them based on the phase three data for medical like acid from the ploy study have an incomplete or inadequate response.
And they they can actually have a worsening of their itch and so adding visa five ray to gain both greater response on biochemical markers of disease as well as.
Alleviate those symptoms of pure riotous I think is a sound strategy from our perspective, when we look at either the visa five writer importantly, just the Seladelpar data on top of you D. C. A we think that just U D. C. A plus seladelpar in fact can meet a significant proportion of patient needs or.
Around biochemical markers of disease progression as well as an H.
So I think from our perspective, our priority is first to get through this initial data set.
Which we believe may be the most robust data set and most compelling data set for a preferred second line treatment alternative of choice. One that can also as we've talked about perhaps demonstrate benefit and a much broader patient population those with still elevated alcuin phosphatase, even if not above 1.67 times the upper.
A limit of normal who can benefit is Chuck mentioned even from normalization.
There's no question that at some point down that line. There may in fact be patients, whose al classes still elevated and could use a further decrease in risk of disease progression I think at that point in time thinking through combinations for what that patient population may be as something that that will continue debate safe to stay.
To our goal is to get Seladelpar in the hands of as many patients that will benefit we've not yet to date J done any combinations per se preclinically with seladelpar in this type of setting.
Okay, great. Thank you <unk>, maybe if I could.
Squeeze in one follow up question to your comment about portal hypertension could you maybe talk about the potential utility of seladelpar in reducing portal hypertension, either in patients with P. B C or perhaps secondary to other forms of liver disease.
Yeah, maybe I can try to sketch out some thoughts that I wouldn't qualify to begin with as being somewhat speculative because we don't have it we don't have any data.
One of the first and most uhm compelling datasets that looked at portal hypertension in patients with PVC was a publication that came out of the.
The group in Montreal, and as well as in Paris that examined the effects of U D. C. A treatment of patients with P. B C and portal hypertension was a very it's not a study that could be done again, it's it was a very invasive study where they measured.
Pressures in both the paddock artery and the panic vein and so they actually measured portal hypertension as opposed to the wedge measures, which are also invasive that are used today. This study is very interesting J in the sense that they actually showed that insignificant number of patients that U D say actually halted progress.
And in fact in some cases improved portal hypertension, there was a subset of patients in that study. There about 30, who were studied for two years placebo versus U D C. A and it did improve their portal hypertension.
So it's a bit of an extrapolation at this point, but I think it gives one.
An example, where an intervention actually affected the portal hypertension. So that's something that I think would be interesting for us to monitor of course, we wouldn't do it in the same way. This study did we would probably be examining another clinical.
Evidence clinical surrogates with you would say for a portal hypertension.
Great. That's helpful. Thank you very much for taking all the questions.
Thank you J.
Our next question is from <unk> be Riley. Please proceed with your question.
Hey, Tim Good afternoon. This is us auto caused me on for my Thanks for taking our questions a number of them, but answered, but maybe just one last one related to the abstract coming up at a S. L D, particularly given that you're you're starting to see sort of similar results in compensated cirrhotic spend on cirrhotic patients can you talk about some of our relationship to establish.
With the both the patient and medical community and how you kind of plan on the and sort of an education campaign on the fact that there can be a real benefit in the cirrhotic population, particularly following the narrowed label of a caliber.
Yeah. Thank you for that question Sahil, maybe I'll ask Dennis to give some of his perspective is you know as our chief Medical officer as he interacts with P eyes, and and patients, giving some of that experience.
Sure. Thanks for Ya Yeah.
Yeah that point has not been lost on Ah T I's or principal investigators already as we interact and engage our principal investigators involved in response Anna sure. They.
Alrighty I appreciate.
<unk> that that particular advantage to solve all power has in patients with compensated cirrhosis.
Which is something that that patients really don't have much of an option at this point.
It's actually one of the driving forces for getting patients into our study in those particular patients. So we hope to be able to show and demonstrate this in response.
As well as Miss sure, although sure as an uncontrolled study.
And and I'm, assuming that we are able to have that data N. R label any agreement with the F. D. A we will certainly be making that educational point as we roll out so ballpark for patients with P. B C.
Alright. Thank you I look forward to the presentation. Thanks for taking my question.
Exactly.
Yeah.
Our next question is from Ed or say with H C. Wainwright. Please proceed with your question.
Alright for what it does is Thomas Oscar in a couple of questions for US first congratulations on the park Rushworth response on the shore so far.
Perhaps the first question regarding the response trial can you tell us what is the target number of clinical sites in the study and approximately what percentage of sites happens row patients past screeners stage so far.
Yeah. Thanks for the question Thomas So you know in enhance we actually had a target that was north of 100 sites. The idea here is the same in fact I can tell you are targeting more sites when we targeted ultimately and enhance and not uncommon in this type of setting we get sites activate it and some.
In fact may not enroll by the time the study fully completes enrollment, but that really doesn't stop us from finding places, where we believe patients can benefit and sites can actually contribute patients. So it's a number even north of where we sit today you can see them Clinton trials Dot Gov. We've got 105 five sites that are active now we expect more to be active between the.
Between now and even the end of this year and we think that's a really important testament around our ability to conduct a global study that gives us confidence around getting this study fully ultimately fully enrolled so we don't provide granularity around specific sites that have actually enrolled patients. Thus far you know I can tell you.
This we interact with sites on a constant basis up and down the organization here it seem of a myself chalk Dennis many of the others in clinical operations have daily if not weekly meetings with sites all around the world and those are really to try to identify some of the challenges sites have had whether their internal resourcing chat.
Jynges opportunities, we might have to find referrals in and around geographic regions for sites.
So there's no question that in some cases, there are clearly patients that come in soon after sites are activated and in other cases, where their sites that may have a few weeks before they bring in a patient for screening. So it's really just a broad effort and we like I said before we've done this before so we know the types of things.
That can help sites at the end of the day, but this is a rare disease again I'll emphasize I I won't you know paint a different picture here for you. It's a rare disease and you know in some cases, a physician who saw two patients you know in 2019 may not see a P. B C patient in 2020, but much of the work that we've done with our C. R O really.
Hankers on our prior experience of understanding Ah centers that have been you know good contributors to clinical studies and will continue that effort.
[noise] understood. Thanks, Thanks for the attitude. So Ah response, perhaps one question of our sure are open right. The long term can you tell us where approximately what is the longest treatment duration of our patients and assure right now and and there's the plan for a short trip report.
Theater actor Ah responses top library, though.
Yeah, So maybe I'll start off and Dennis please jumping here at my conclusion and provide any additional color that I may have missed so sure Thomas actually really kicked off earlier this year I want to say it was February of this year and so as sites continue.
To come on board those that study is for patients that had been on previous studies would sell Adele parse our previous phase two studies as well as our previous enhance phase three study.
So there's a bit of a restart for many of those patients because we had paused development and paused or prior longterm study, but I think what's most important is in our prior longterm study as we've as you'll see it a S. L. D. About 50 patients that have been through two years of treatment, we actually had a subset of P.
<unk>, even out to three years of treatment. So in terms of continuous treatment I'd say that we had probably a little over a dozen or so patients that were out to three years.
And we continue to see consistent benefit across the biochemical markers of disease, even for those patients much smaller subset. So we're focusing this presentation on a good 50 patients sub set out to two years, but assure you know real really feed N and continue to contribute to that long term safety.
We will not only have long term safety out of a sure by the time, we file our N D. A at the completion of the response study.
But of course will continue to gather additional data around efficacy and patient benefit. So it's a very incredibly valuable data set in as as we mentioned in our prepared remarks really the only study today of its kind for those programs that are currently in development for P. B C and we think it really adds breath.
Yep, so the overall Seladelpar program.
Yeah, and also not only adding database to solve all kind of programs.
But also.
Hurting the trust of the patients that continued to take the drug and open label setting as.
As well as having principal investigators accumulate clinical experience with a with a drug.
I think we will only help us in the long run.
No just maybe add one other thing Thomas <unk>, you're you're kind of getting at the operational aspects of assure when you're asking about length of treatment just just to point out a key distinction between ensuring response.
For sure is really going back to sites, we were already operating at and patients had to be in a prior study. So it's not a matter of going and searching for patients. It just contacting them you know confirming their interests getting them scheduled in in enrolling so the ability to get patients back into it sure is is a little bit.
<unk>.
Uhm process and it's frankly, it's easier.
Okay understood, perhaps 111 final follow up off the response there.
So so you mentioned of course, giving patients back in Turkey assure study after apartments treatments instead, they plan to look at all.
Hopefully lost Thomas there.
Yeah, I don't hear.
Okay, I can see if I can get him back but in the meantime, I'd like to introduce Alicia Uhm Cantor Fitzgerald wish for her question. Please proceed.
Hi, This is Emily unfriendly theory, thanks for taking a question I'm just curious on based on your conversations with physicians, who are treating PVC patients how would you characterize the opportunity for patients currently taking a calvin maybe they're not getting benefit from it or could be better served and how do you think solids out Parkinson's slot population.
Thank you.
Yeah look I think it's a great question Emily and once again at the conclusion of his remarks, Dennis please jump in with any of the experience you've had thus far.
You know I think the the challenges without calibre are are fairly well known but putting that aside just for a moment for those patients.
That of course are experiencing biochemical a benefit in response and are not actually experiencing edge you.
You know, it's unreasonable to have a physician really move that patient off of treatment, that's actually providing them benefit without further challenges that we know if you look at the data sets from <unk> phase two and phase III studies that a fairly significant number of patients that actually do either experienced H or have an exacerbation of H.
That's really one of the key issues.
But even beyond that there are patients that nevertheless, also have an inadequate biochemical response, and we've seen patients either on prior treatment without kalvar off label fibroids come onto Seladelpar and actually have an improved benefit on biochemical markers of disease and so at easel for.
Example, we actually had an abstract that demonstrated a number of the patients.
Advocacy as well as overall tolerability data those are patients that had prior experience with a medical like acid or five rates, where we see a very comparable effect with seladelpar in those patients as we've seen with patients that haven't tried those treatment alternatives before so you know.
Anecdotally I'll emphasize that this is anecdotal, but we do see physicians, who have patience is inadequate responders or intolerant to medical like acid.
Look to move those patients they'd have to wash off before they come into response, but they can in fact enroll in response wash off treatment for 90 days and we do actually C. P is enrolling those patients into our current phase III study.
Yeah.
By saying that you know my one of my recent interactions with a clinician.
Taught me something you're interested in which is that uhm, but for writers may be something that patients don't talk about very actively with their with their clinicians or their healthcare providers.
Uhm. This this mission told me that you know the patient never mentioned for writers got placed on <unk>, but later on down the road.
The <unk> the the the physician learn but the patient did in fact have for writers some fatigue sleep disturbance and had he known maybe he wouldn't have made that decision to place the patient will calibre and perhaps the patients would have been a better candidate for a response study. So it's a it's a it's a long way or.
Saying that we need to educate patients as well as physicians on this particular aspect of Seladelpar and how it can be very divergent from the profile that caliber house.
Okay. Our next question is from Tom Smith with S. D. P. Leerink. Please proceed with your question.
Hi, everyone. This is Mike M for Tom Thanks for taking my question.
Just curious do you have a sense of what portion of patients in the face of yours on study have opted to receive a liver biopsy and just as a follow up could there be a scenario in which you can only enrolled patients that are willing to receive a liver biopsy. After a certain point, just you're able to be aligned with the amount of biopsies that the F. D. A is expecting to see.
Mike I I didn't quite get the second part of the question, but maybe chucked. It let me at least first address your ear first question. So we of course recognize which patients are volunteering for biopsy at the outset, you know that's not a number again that we would report I will say that N.
Or enhance study we had at least 16% of patients volunteer for a biopsy going into response, we further emphasize the benefit for patients to learn about the stage of their disease and progression of their disease. So fundamentally we're confident that we're gonna get the patience, we need to volunteer for a biopsy and this.
Study because it's been much more of a conscious effort for us as we've enrolled responses. When we did even enhanced so I think can things continue to track well in those conversations, but we don't specifically report those those numbers as we're enrolling the study, but we're quite confident.
In our obligation to patients as well as to regulators as we look to complete response.
Just to your second part of your question just reinforce wood Soochow said I personally.
Mm don't believe there's gonna be any problem with meeting the threshold.
We'll need to deliver for to the regulators, but I suppose theoretically if it turned out that we thought there was an issue. We my basically take the approach where we we could consider requiring it but I just don't think that's gonna come past. So I think we're we're not anywhere close to that situation right now.
Got it that's really helpful. Thanks, and then just take one in terms of the investigator sponsored phase two study of M. B X 29, 82 could topline results is still come before year end or is that something we're more likely to maybe early.
First half 2022.
Yeah. So you know a good question, Mike we expect that study to complete and ultimately have data sometime next year.
So once again, that's the study that's being fully funded by the chop the Helmsley charitable trust.
Conducted by a single sites C. R O in Florida add Unhealth T. R I where of course in close contact with them in the <unk>. The study continues to progress we're excited about that potential data potential opportunity to do something quite novel for patients with type one diabetes, who are suffering from hypoglycemia, but I think fundamentally.
That data set would come at some point as the study is completed next year.
Okay got it thanks very much.
Okay. Thank you.
Ladies and gentlemen, we have reached the end of the question and answer session and I would like to turn the call back over to shoot jump shots for closing remarks.
Thank you operator.
I hope today, you walk away with an appreciation for our focus.
<unk>, what we believe is the most robust development program and PVC today, and our excitement around the opportunity Seladelpar has to be a leading impactful treatment alternative to a broad population of patients with PVC.
We have enrolled multiple global phase two and phase three studies and P. B C. In the past and are confident in our ability to do it once again.
We know the need for patience is now and all of our efforts and focus is on this execution.
We also couldn't be more excited to have another meaningful presence at the liver meeting at the end of this week.
And believe the data we have to share will continue to differentiate seladelpar in the setting of PVC.
Thank you once again.
This concludes today's conference. He may disconnect. Your lines at this time. Thank you for your participation.
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